Summary
Background
Globally, chronic hepatitis B (CHB) is a major public health concern. Timely and effective management can prevent disease progression to cirrhosis and reduce the risk of ...hepatocellular carcinoma (HCC). Currently, there is no consensus on the clinical management of CHB in East Asia.
Aim
To establish an East Asia expert opinion on treatment initiation for CHB based on alanine aminotransferase (ALT) level, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, cirrhosis and HCC risk scores.
Methods
A meeting was held online with a panel of 10 experts from East Asia to discuss ALT, HBV DNA, cirrhosis and HCC risk scores. Indications for CHB treatment in the latest international guidelines were reviewed. Consensus was summarised to provide recommendations on the initiation of treatment for CHB.
Results
Anti‐viral therapy is recommended for CHB patients with (a) HBV DNA ≥ 2000 IU/mL and ALT ≥ 1× upper limit of normal (ULN); (b) HBV DNA ≥ 2000 IU/mL, ALT < 1× ULN and ≥ F2 fibrosis and/or ≥ A2 necroinflammation occurs; (c) cirrhosis and detectable HBV DNA; or (d) HBV DNA ≥ 2000 IU/mL, ALT < 1× ULN and a family history of cirrhosis or HCC, extrahepatic manifestations or age > 40 years. Patients with cirrhosis and/or HCC should be treated regardless of ALT levels if HBV DNA level is detectable. Initiating anti‐viral therapy or close monitoring at 3‐month intervals is recommended for CHB patients with at least two HCC risk factors.
Conclusions
These expert recommendations will contribute to a new standard of daily clinical practice in East Asia.
Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia‐Pacific region. Many areas in ...the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations.
Aims
To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality.
Methods
A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long‐term trends in NAFLD incidence.
Results
In the areas studied, prevalent NAFLD cases were projected to increase 6%‐20% during 2019‐2030, while prevalent NASH cases increase 20%‐35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%‐85%, while incident decompensated cirrhosis cases increase 65%‐100% by 2030. Likewise, NAFLD‐related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality.
Conclusions
Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD‐related disease burden in the Asia‐Pacific region.
In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing ...evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.
Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike ...protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.
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•The furin cleavage site in the SARS-CoV-2 spike protein mediates syncytium formation•The SARS-CoV-2 spike-mediated syncytium is suppressed by specific furin inhibitors•Furin inhibitors block SARS-CoV-2 virus entry and virus replication•Furin inhibitors are potential antiviral agents for SARS-CoV-2 infection and pathogenesis
Development of effective antiviral agents is an urgent unmet need for SARS-CoV-2 infection. Cheng et al. find that cleavage of the furin substrate site in the viral spike protein is critical for virus production and cytopathic effects. Two inhibitors targeting furin are potential antiviral agents to control SARS-CoV-2 infection and pathogenesis.
Purpose To construct a nomogram with the albumin-bilirubin (ALBI) grade to assess the long-term outcomes of patients with early-stage hepatocellular carcinoma (HCC) after radiofrequency ablation ...(RFA). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. We studied 622 treatment-naïve patients with HCC according to the Milan criteria who subsequently underwent RFA from 2002 to 2013. Baseline characteristics were collected to identify the risk factors for determination of poor overall survival after RFA. The multivariate Cox proportional hazards model based on significant prognostic factors of overall survival was used to construct the nomogram. Results After a median follow-up time of 35.7 months, 190 patients had died. The cumulative 5- and 10-year overall survival rates were 63.1% and 48.7%, respectively. Stratified according to ALBI grade, the cumulative 5- and 10-year survival rates were 80.0% and 67.9% for patients with grade 1, respectively, and 48.6% and 35.1% for those with grades 2-3, respectively (P < .001). Multivariate analysis results showed that patient age older than 65 years, a prothrombin time international normalized ratio greater than 1.1, α-fetoprotein level greater than 20 ng/mL, multiple tumors, and ALBI grade 2 or 3 were associated with overall mortality. A nomogram was developed on the basis of these five variables. Internal validation with 200 bootstrapped sample sets had a good concordance index of 0.770 (95% confidence interval: 0.633, 0.876). Conclusion This simple nomogram based on the ALBI grade offers personalized long-term survival data for patients with early-stage HCC who undergo RFA.
RSNA, 2017 Online supplemental material is available for this article.
A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO
(42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, ...transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.
To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the ...interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19.
Synopsis
Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.
The ACE2‐Fc fusion protein can form a dimer that mimics a humanized antibody and specifically binds to the SARS‐CoV‐2 Spike protein.
The ACE2‐Fc fusion protein abrogates virus replication by blocking SARS‐CoV‐2 entry in clinical isolates.
The peptidase activity of ACE2‐Fc enables the decoy antibody to reduce angiotensin II‐mediated cytokine cascade.
After binding to Spike‐expressing target cells, ACE2‐Fc activates degranulation of NK cells.
Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.
Objective
Whether oral lichen planus (OLP) was potentially malignant remains controversial. Here, we examined associations of ZNF582 methylation (ZNF582m) with OLP lesions, dysplastic features and ...squamous cell carcinoma (OSCC).
Materials and Methods
This is a case–control study. ZNF582m was evaluated in both lesion and adjacent normal sites of 42 dysplasia, 90 OSCC and 43 OLP patients, whereas ZNF582m was evaluated only in one mucosal site of 45 normal controls. High‐risk habits affecting ZNF582m such as betel nut chewing and cigarette smoking were also compared in those groups.
Results
OLP lesions showed significantly lower ZNF582m than those of dysplasia and OSCC. At adjacent normal mucosa, ZNF582m increased from patients of OLP, dysplasia, to OSCC. In addition, ZNF582m at adjacent normal sites in OLP patients was comparable to normal mucosa in control group. Dysplasia/OSCC patients with high‐risk habits exhibited significantly higher ZNF582m than those without high‐risk habits. However, ZNF582m in OLP patients was not affected by those high‐risk habits.
Conclusions
OLP is unlikely to be potentially malignant based on ZNF582m levels. ZNF582m may also be a potential biomarker for distinguishing OLP from true dysplastic features and OSCC, and for monitoring the malignant transformation of OLP, potentially malignant disorders with dysplastic features and OSCC.
Scaffolds in games have the potential to facilitate learning effects in addition to assisting the gaming process. However, studies on game-based science learning usually only adopt questionnaires to ...evaluate scientific concepts, and use interviews or observations to assess problem solving ability, neglecting the importance of investigating game-making outcomes. We customized a digital game, “Crayon Physics Deluxe,” with varied scaffolding designs to evaluate their effects on science learning. A total of 126 participants were divided into four groups: demonstration scaffolding, non-scaffolding, marking critical features scaffolding, and the no-game group. Learning outcomes were examined in terms of physics knowledge acquisition (in the form of concept maps) and design creativity (in the form of game episode designs). Students were asked to transform their roles from problem solvers to problem designers, which might not only demonstrate their ability to solve scientific problems, but also develop their creativity potential in designing scientific puzzles. The results indicated that the marking critical features scaffolding group performed significantly better than the demonstration scaffolding group in both conceptual knowledge acquisition and the sensitivity dimension of design creativity, while the group with demonstration scaffolding scored higher in the flexibility dimension of design creativity. These findings suggest that proper scaffolds could be designed to function as learning scaffolds rather than just as gaming scaffolds, and different learning purposes require various scaffolding designs. The content of the scaffolds, as well as the timing of their provision should be carefully designed according to the game features to achieve specific instructional purposes.
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•Customized digital games have the potential to meet specific teaching goals.•Appropriate scaffolding could enhance knowledge acquisition & design creativity.•Concept maps and game design outcomes were used to assess learning effects.•Scaffolding types and timing should be considered when customizing digital games.
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